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Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Myelofibrosis with Prior Exposure to Janus Kinase 1/2 Inhibitors. Biol Blood Marrow Transplant 2016 Mar;22(3):432-40 PMID: 26493563 PMCID: PMC5030817

Pubmed ID

26493563

DOI

10.1016/j.bbmt.2015.10.005

Abstract

The impact of Janus kinase (JAK) 1/2 inhibitor therapy before allogeneic hematopoietic cell transplantation (HCT) has not been studied in a large cohort in myelofibrosis (MF). In this retrospective multicenter study, we analyzed outcomes of patients who underwent HCT for MF with prior exposure to JAK1/2 inhibitors. One hundred consecutive patients from participating centers were analyzed, and based on clinical status and response to JAK1/2 inhibitors at the time of HCT, patients were stratified into 5 groups: (1) clinical improvement (n = 23), (2) stable disease (n = 31), (3) new cytopenia/increasing blasts/intolerance (n = 15), (4) progressive disease: splenomegaly (n = 18), and (5) progressive disease: leukemic transformation (LT) (n = 13). Overall survival (OS) at 2 years was 61% (95% confidence interval [CI], 49% to 71%). OS was 91% (95% CI, 69% to 98%) for those who experienced clinical improvement and 32% (95% CI, 8% to 59%) for those who developed LT on JAK1/2 inhibitors. In multivariable analysis, response to JAK1/2 inhibitors (P = .03), dynamic international prognostic scoring system score (P = .003), and donor type (P = .006) were independent predictors of survival. Among the 66 patients who remained on JAK1/2 inhibitors until stopped for HCT, 2 patients developed serious adverse events necessitating delay of HCT and another 8 patients had symptoms with lesser severity. Adverse events were more common in patients who started tapering or abruptly stopped their regular dose ≥6 days before conditioning therapy. We conclude that prior exposure to JAK1/2 inhibitors did not adversely affect post-transplantation outcomes. Our data suggest that JAK1/2 inhibitors should be continued near to the start of conditioning therapy. The favorable outcomes of patients who experienced clinical improvement with JAK1/2 inhibitor therapy before HCT were particularly encouraging, and need further prospective validation.

Author List

Shanavas M, Popat U, Michaelis LC, Fauble V, McLornan D, Klisovic R, Mascarenhas J, Tamari R, Arcasoy MO, Davies J, Gergis U, Ukaegbu OC, Kamble RT, Storring JM, Majhail NS, Romee R, Verstovsek S, Pagliuca A, Vasu S, Ernst B, Atenafu EG, Hanif A, Champlin R, Hari P, Gupta V

Authors

Parameswaran Hari MD Chief, Professor in the Medicine department at Medical College of Wisconsin
Laura Michaelis MD Associate Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-84950996639   39 Citations

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Allografts
Disease-Free Survival
Female
Hematopoietic Stem Cell Transplantation
Humans
Janus Kinase 1
Janus Kinase 2
Middle Aged
Primary Myelofibrosis
Protein Kinase Inhibitors
Retrospective Studies
Survival Rate
jenkins-FCD Prod-331 a335b1a6d1e9c32173c9534e6f6ff51494143916